Variants are the results of the exposure of patients from theMount Massive Asylum to the Morphogenic Engine created by former Nazi scientist Dr. Rudolf Wernicke. The after-effects of the therapy altered their mind and provoked physical deformities. The outcomes of those after-effects can't be determined, thus giving to those afflicted the name of Variants.

Most of the Variants have pale skin and mutilations, likely having to do with the experiments they were once exposed to. They differ in ways that some are thin and weak, while others are massive and brutally strong, such as Chris Walker, who is a commonly seen Variant in the first game. Their clothing ranges from standard psychiatric attire to ripped and torn shorts. The Twins, however, are naked. There are some Variants that are quite sane, an example being the Variant in the Sewer who questions whether Wernicke is deceased, and the PyromaniacVariant in the Cafeteria in the Male Ward who explains that he would rather die than stay in the asylum, and points Miles towards the exit. There are also other Variants who are not permanently hostile and attack only if the player moves into close proximity, others who assist, or hinder the player with cryptic hints or stories, and Variants who ignore the player completely.

For the most part, the humanity of some of the Variants seems to have left them at some stage during their torture, turning into sadistic, cruel and ruthless pursuers. Others tend to become terrified (e.g. hiding under beds; One that crawls away after attacking you when he jumps from the wheelchair he is sitting on near the beginning), others seem masochistic (e.g. one banging his head into a wall in different places), and a few keep their level of sanity and are slightly helpful. Some Variants seem to be followers of Father Martin.

Among their abilities is their physical strength and stamina; being able to smash doors, pull out organs, destroy reinforced glass and chase after victims. Even though most of them are insane, they still retain some intelligence, proven when they track down Miles' hiding spots, listen for sound and even set up ambushes, such Variants include Richard Trager and The Twins, who are also capable of opening and closing doors.